Use of Alcohol in Anesthesia

Dundee, John W.; Isaac, M.; CLARKE, RICHARD S. J.

doi:10.1213/00000539-196907000-00031

Cited by 20 publications

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“…Ethanol reduces the excitability of central neurons and can be used as an anesthetic. 37,38 The direct application of ethanol to peripheral nerves reduces the amplitude and can even inhibit the conduction of action potentials. 34,39 Ethanol may also facilitate the entry of QX-314 into TRPV1-expressing nociceptors because ethanol activates TRPV1 receptors and potentiates their response to capsaicin.…”

Section: Resultsmentioning

confidence: 99%

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Differential Effects of Peripheral versus Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats

2012

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Background Neuropathic pain is common and difficult to treat. Recently a technique was developed to selectively inhibit nociceptive inputs by simultaneously applying two drugs: capsaicin, a transient receptor potential vanilloid receptor 1 channel activator and QX-314, a lidocaine derivative that intracellularly blocks sodium channels. We used this technique to investigate whether transient receptor potential vanilloid receptor 1-expressing nociceptors contribute to neuropathic pain. Methods The rat chronic constriction injury model was used to induce neuropathic pain in order to test the analgesic effects of both peripheral (perisciatic) and central (intrathecal) administration of the QX-314/capsaicin combination. The Hargreaves and von Frey tests were used to monitor evoked pain-like behaviors and visual observations were used to rank spontaneous pain-like behaviors. Results Perisciatic injections of the QX-314/capsaicin combination transiently increased the withdrawal thresholds by ~3 fold for mechanical and thermal stimuli in rats (n = 6/group) with nerve injuries suggesting that peripheral transient receptor potential vanilloid receptor 1-expressing nociceptors contribute to neuropathic pain. In contrast, intrathecal administration of the QX-314/capsaicin combination did not alleviate pain-like behaviors (n = 5/group). Surprisingly, intrathecal QX-314 alone (n = 9) or in combination with capsaicin (n = 8) evoked spontaneous pain-like behaviors. Conclusions Data from the perisciatic injections suggested that a component of neuropathic pain was mediated by peripheral nociceptive inputs. The role of central nociceptive terminals could not be determined because of the severe side effects of the intrathecal drug combination. We concluded that only peripheral blockade of transient receptor potential vanilloid receptor 1-expressing nociceptive afferents by the QX-314/capsaicin combination was effective at reducing neuropathic allodynia and hyperalgesia.

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Section: Resultsmentioning

confidence: 99%

“…In addition, unlike ethanol, DMSO does not have anesthetic effects at the concentrations used in this study. 32,37,38 …”

Section: Resultsmentioning

confidence: 99%

Differential Effects of Peripheral versus Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats

2012

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“…Ethanol may have been the oldest means to achieve general anesthesia in man (Dundee et al, 1969). Like many other general anesthetics, ethanol acts on multiple cellular and molecular sites (Franks and Lieb, 1994;Wong et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Differential sensitivities of TTX-resistant and TTX-sensitive sodium channels to anesthetic concentrations of ethanol in rat sensory neurons

Kendig

1998

J. Neurosci. Res.

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Ethanol at concentration of 200 mM induces anesthesia in experimental animals and depresses neurotransmission in isolated spinal cords. To determine whether actions on primary afferent nerve terminals contribute to ethanol's depressant effects on spinal cord, a study was undertaken to test whether ethanol blocks sodium currents (I(Na)) in dorsal root ganglion neurons (DRGn). Whole-cell patch clamp was used to examine I(Na) in DRGn isolated from 1- to 15-day-old rats. At a holding potential of -80 mV ethanol (200 mM) decreased peak tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) I(Na) by 19.0% +/- 2.7 (mean +/- SEM) and 8.5% +/- 2.2, respectively. Maximal available I(Na) was reduced to 82 +/- 4% (TTX-R) and 93 +/- 1% (TTX-S) of control. Steady-state inactivation curves were shifted in the hyperpolarizing direction by 2.1 +/- 0.2 mV (TTX-R) and 1.1 +/- 0.1 mV (TTX-S). At prepulse potentials of -30 mV (TTX-R) and -70 mV (TTX-S), these shifts contributed an additional 17 +/- 1% (TTX-R) and 7 +/- 1% (TTX-S) reduction in available I(Na). Ethanol thus selectively induced both voltage-independent and voltage-dependent block of TTX-R I(Na) in DRGn. Because DRGn TTX-R sodium channels are associated with small-diameter primary afferent fibers, these results are consistent with a role for ethanol actions on sodium channels in depression of nociceptive-related neurotransmission in spinal cord.

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“…n-Alcohols can produce a state of general anesthesia, historically ethanol has been used for this purpose (Dundee et al, 1969), and there is evidence that ethanol and other alcohols inhibit sodium channel function. For example, a high concentration of ethanol (500 mM) inhibited sodium influx in synaptosomes isolated from rodent brain (Harris and Bruno, 1985), and Wu and Kendig (1998) showed that tetrodotoxin (TTX)-resistant and TTX-sensitive sodium channels in rat DRG neurons are inhibited by ethanol (50 -200 mM) (Wu and Kendig, 1998).…”

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n-Alcohols Inhibit Voltage-Gated Na⁺ Channels Expressed in Xenopus Oocytes

Horishita

Harris²

2008

J Pharmacol Exp Ther

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Voltage-gated sodium channels are essential for the initiation and propagation of action potentials in excitable cells and are known as a target of local anesthetics. In addition, inhibition of sodium channels by volatile anesthetics has been proposed as a mechanism of general anesthesia. The n-alcohols produce anesthesia, and their potency increases with carbon number until a "cut-off" is reached. In this study, we examined effects of a range of n-alcohols on Na v 1.2 subunits to determine the alcohol cut-off for this channel. We also studied the effect of a short-chain alcohol (ethanol) and a long-chain alcohol (octanol) on Na v 1.2, Na v 1.4, Na v 1.6, and Na v 1.8 subunits, and we investigated the effects of alcohol on channel kinetics. Ethanol and octanol inhibited sodium currents of all subunits, and the inhibition of the Na v 1.2 channel by n-alcohols indicated a cut-off at nonanol. Ethanol and octanol produced open-channel block, which was more pronounced for Na v 1.8 than for the other sodium channels. Inhibition of Na v 1.2 was due to decreased activation and increased inactivation. These results suggest that sodium channels may have a hydrophobic binding site for n-alcohols and demonstrate the differences in the kinetic mechanisms of inhibition for n-alcohols and inhaled anesthetics.

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Use of Alcohol in Anesthesia

Cited by 20 publications

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Differential Effects of Peripheral versus Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats

Differential Effects of Peripheral versus Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats

Differential sensitivities of TTX-resistant and TTX-sensitive sodium channels to anesthetic concentrations of ethanol in rat sensory neurons

n-Alcohols Inhibit Voltage-Gated Na⁺ Channels Expressed in Xenopus Oocytes

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Use of Alcohol in Anesthesia

Cited by 20 publications

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Differential Effects of Peripheral versus Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats

Differential Effects of Peripheral versus Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats

Differential sensitivities of TTX-resistant and TTX-sensitive sodium channels to anesthetic concentrations of ethanol in rat sensory neurons

n-Alcohols Inhibit Voltage-Gated Na+ Channels Expressed in Xenopus Oocytes

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n-Alcohols Inhibit Voltage-Gated Na⁺ Channels Expressed in Xenopus Oocytes